title: Asymmetric migration of human keratinocytes under mechanical stretch and cocultured fibroblasts in a wound repair model.
abstract: Keratinocyte migration during re-epithelization is crucial in wound healing under biochemical and biomechanical microenvironment. However, little is known about the underlying mechanisms whereby mechanical tension and cocultured fibroblasts or keratinocytes modulate the migration of keratinocytes or fibroblasts. Here we applied a tensile device together with a modified transwell assay to determine the lateral and transmembrane migration dynamics of human HaCaT keratinocytes or HF fibroblasts. A novel pattern of asymmetric migration was observed for keratinocytes when they were cocultured with non-contact fibroblasts, i.e., the accumulative distance of HaCaT cells was significantly higher when moving away from HF cells or migrating from down to up cross the membrane than that when moving close to HF cells or when migrating from up to down, whereas HF migration was symmetric. This asymmetric migration was mainly regulated by EGF derived from fibroblasts, but not transforming growth factor α or β1 production. Mechanical stretch subjected to fibroblasts fostered keratinocyte asymmetric migration by increasing EGF secretion, while no role of mechanical stretch was found for EGF secretion by keratinocytes. These results provided a new insight into understanding the regulating mechanisms of two- or three-dimensional migration of keratinocytes or fibroblasts along or across dermis and epidermis under biomechanical microenvironment.
authors.affiliation: Key Laboratory of Microgravity (National Microgravity Laboratory), Institute of Mechanics, Chinese Academy of Sciences, Beijing, China ; Center of Biomechanics and Bioengineering, Institute of Mechanics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Dongyuan
authors.initials: D
authors.lastname: Lü
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Liu
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Gao
authors.forename: Bo
authors.initials: B
authors.lastname: Huo
authors.forename: Yingyong
authors.initials: Y
authors.lastname: Kang
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Shujin
authors.initials: S
authors.lastname: Sun
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Luo
authors.forename: Mian
authors.initials: M
authors.lastname: Long
mesh_terms: D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects; D018920:Coculture Techniques; D024042:Collagen Type I / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000473:pathology*; D008954:Models, Biological; D013314:Stress, Mechanical; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D024042:Collagen Type I; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor